Controllable release nasal system

ABSTRACT

Embodiments of devices and system for controllable nasal delivery of materials are described. Methods of use of such devices and system and software for controlling the operation of such devices and systems are also disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to and claims the benefit of theearliest available effective filing date(s) from the following listedapplication(s) (the “Related Applications”) (e.g., claims earliestavailable priority dates for other than provisional patent applicationsor claims benefits under 35 USC § 119(e) for provisional patentapplications, for any and all parent, grandparent, great-grandparent,etc. applications of the Related Application(s)).

Related Applications:

-   -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 10/949,186, entitled A CILIATED        STENT-LIKE SYSTEM, naming Richa Wilson, Victoria Y. H. Wood, W.        Daniel Hillis, Clarence T. Tegreene, Muriel Y. Ishikawa, and        Lowell L. Wood, Jr. as inventors, filed 24 Sep. 2004, which is        currently co-pending, or is an application of which a currently        co-pending application is entitled to the benefit of the filing        date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 10/827,576, entitled A SYSTEM FOR        PERFUSION MANAGEMENT, naming Lowell L. Wood, Jr. as inventor,        filed 19 Apr. 2004, which is currently co-pending, or is an        application of which a currently co-pending application is        entitled to the benefit of the filing date.    -   For purposes of the USPTO extra-statutory requirements, the        present application constitutes a continuation-in-part of U.S.        patent application Ser. No. 10/827,578, entitled A SYSTEM WITH A        SENSOR FOR PERFUSION MANAGEMENT, naming Lowell L. Wood, Jr. as        inventor, filed 19 Apr. 2004, which is currently co-pending, or        is an application of which a currently co-pending application is        entitled to the benefit of the filing date. For purposes of the        USPTO extra-statutory requirements, the present application        constitutes a continuation-in-part of United U.S. patent        application Ser. No. 10/827,572, entitled A SYSTEM WITH A        RESERVOIR FOR PERFUSION MANAGEMENT, naming Lowell L. Wood, Jr.        as inventor, filed 19 Apr. 2004, which is currently co-pending,        or is an application of which a currently co-pending application        is entitled to the benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 10/827,390, entitled A TELESCOPING PERFUSIONMANAGEMENT SYSTEM, naming Lowell L. Wood, Jr. as inventor, filed 19 Apr.2004, which is currently co-pending, Or is an application of which acurrently co-pending application is entitled to the benefit of thefiling date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 11/403,230, entitled LUMENALLY-ACTIVE DEVICE,naming Bran Ferren, W. Daniel Hillis, Roderick A. Hyde, Muriel Y.Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold, Elizabeth A. Sweeney,Clarence T. Tegreene, Richa Wilson, Lowell L. Wood, Jr. and Victoria Y.H. Wood as inventors, filed 12 Apr. 2006, which is currently co-pending,or is an application of which a currently co-pending application isentitled to the benefit of the filing date.

The United States Patent Office (USPTO) has published a notice to theeffect that the USPTO's computer programs require that patent applicantsreference both a serial number and indicate whether an application is acontinuation or continuation-in-part. Stephen G. Kunin, Benefit ofPrior-Filed Application, USPTO Official Gazette Mar. 18, 2003, availableat http://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm.The present applicant entity has provided above a specific reference tothe application(s) from which priority is being claimed as recited bystatute. Applicant entity understands that the statute is unambiguous inits specific reference language and does not require either a serialnumber or any characterization, such as “continuation” or“continuation-in-part,” for claiming priority to U.S. patentapplications. Notwithstanding the foregoing, applicant entityunderstands that the USPTO's computer programs have certain data entryrequirements, and hence applicant entity is designating the presentapplication as a continuation-in-part of its parent applications as setforth above, but expressly points out that such designations are not tobe construed in any way as any type of commentary and/or admission as towhether or not the present application contains any new matter inaddition to the matter of its parent application(s).

All subject matter of the Related Applications and of any and allparent, grandparent, great-grandparent, etc. applications of the RelatedApplications is incorporated herein by reference to the extent suchsubject matter is not inconsistent herewith.

BACKGROUND

Devices and systems have been developed for use in various body lumens,particularly in the cardiovascular system, digestive, and urogenitaltract. Catheters are used for performing a variety of sensing andmaterial delivery tasks. Stents are implanted in blood vessels for thepurpose of preventing stenosis or restenosis of blood vessels. Capsulescontaining sensing and imaging instrumentation, that may be swallowed bya subject and which travel passively through the digestive tract havealso been developed. Robotic devices intended to move through the lowerportion of the digestive tract under their own power are also underdevelopment.

SUMMARY

The present application describes devices, systems, and related methodsfor delivery of a material to a nasal region of a subject. Embodimentsof delivery devices and systems for placement within a nasal region aredisclosed. In one aspect, a system includes but is not limited to astructural element including a positioning portion configured forcontacting an interior surface of a nasal region and mounting thestructure element within the nasal region of a subject, a deliveryportion mounted relative to the structural element and configured torelease at least one material responsive to a delivery control signal,and control signal generation circuitry configured to generate adelivery control signal corresponding to a desired pattern of release ofthe at least one material into the nasal region. In addition to theforegoing, other system aspects are described in the claims, drawings,and text forming a part of the present disclosure.

In one aspect, a method includes but is not limited to releasing atleast one material from a delivery portion of a delivery device mountedwithin a nasal region of a subject in response to a delivery controlsignal corresponding to a desired release pattern. The method mayinclude sensing a parameter of interest in the nasal region with asensor in the delivery device and controlling the release of the atleast one material based upon the value of the parameter of interest. Insome aspects, the method may include generating the delivery controlsignal. In addition to the foregoing, other method aspects are describedin the claims, drawings, and text forming a part of the presentdisclosure.

Various aspects of the operation of such delivery devices may beperformed under the control of hardware, software, firmware, or acombination thereof. In one or more various aspects, related systemsinclude but are not limited to circuitry and/or programming foreffecting the herein-referenced method aspects; the circuitry and/orprogramming can be virtually any combination of hardware, software,and/or firmware configured to effect the herein referenced methodaspects depending upon the design choices of the system designer.Software for operating a delivery device according to variousembodiments is also described.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a side cross-sectional view of an embodiment of controllablerelease nasal device emplaced in a nostril;

FIG. 2 is a front cross-sectional illustration of the controllablerelease nasal device depicted in FIG. 1;

FIG. 3 is a detailed view of the controllable release nasal device shownin FIGS. 1 and 2;

FIG. 4 is an illustration of a lumenally active device;

FIG. 5 is an illustration of another embodiment of a controllablerelease nasal device;

FIG. 6 is a front cross-section view of the device of FIG. 5;

FIG. 7 is a further depiction of the device of FIG. 6;

FIG. 8 is a front cross-sectional view of an embodiment of acontrollable release nasal device including a clip;

FIG. 9 is a side cross-sectional view of the embodiment of FIG. 8;

FIG. 10 is a front cross-sectional view of another embodiment of acontrollable release nasal device;

FIG. 11 is a side cross-sectional view of the embodiment of FIG. 10;

FIG. 12 is an illustration of an embodiment of a structural element;

FIG. 13 is an illustration of another embodiment of a structuralelement;

FIG. 14 is an illustration of another embodiment of a structuralelement;

FIG. 15 is an illustration of another embodiment of a structuralelement;

FIG. 16 is an illustration of a further embodiment of a structuralelement;

FIG. 17 is an illustration of another embodiment of a structuralelement;

FIG. 18 is an illustration of another embodiment of a structuralelement;

FIG. 19A and 19B depicted changes in dimension of an embodiment;

FIG. 20 is a cross-sectional view of an embodiment of a structuralelement;

FIG. 21 is a cross-sectional view of another embodiment of a structuralelement;

FIG. 22 is a cross-sectional view of another embodiment of a structuralelement;

FIG. 23 is a cross-sectional view of another embodiment of a structuralelement;

FIG. 24 is a cross-sectional view of another embodiment of a structuralelement;

FIG. 25 is a cross-sectional view of yet another embodiment of astructural element;

FIG. 26 is a front cross-sectional depiction of release of material froma controllable release nasal device;

FIG. 27 is a side cross-sectional view of delivery of material to thenasal mucosa from a controllable release nasal device;

FIG. 28 is a side cross-sectional view of delivery of material to theolfactory region from a controllable release nasal device;

FIG. 29 is a side cross-sectional view of delivery of material towardthe nasopharynx from a controllable release nasal device;

FIG. 30 is an illustration of a device including stored deliverablematerial;

FIG. 31 is an illustration a delivery device including an extension;

FIG. 32 is a cross-sectional view of an embodiment of a device includinga stored deliverable material and a barrier release mechanism;

FIG. 33 is a cross-sectional view of another embodiment of a deviceincluding a stored deliverable material and a barrier release mechanism;

FIGS. 34A and 34B are depictions of the release of a stored deliverablematerial from a reservoir via a rupturable barrier;

FIGS. 35A and 35B are depictions of the release of a stored deliverablematerial from a reservoir via a degradable barrier;

FIGS. 36A and 36B are depictions of the release of a stored deliverablematerial from a reservoir via a barrier having controllablepermeability;

FIGS. 37A and 37B are depictions of the release of a stored deliverablematerial from a carrier material;

FIG. 38 is an illustration of an embodiment of a controllable releasenasal system including an external material source;

FIG. 39 is a close-up illustration of the nasal device portion of thesystem of FIG. 38;

FIG. 40 is a block diagram of a controllable release nasal system;

FIG. 41 is a schematic diagram illustrating components of controlcircuitry of a controllable release nasal system;

FIG. 42 is an illustration of a controllable release nasal systemincluding an external control portion;

FIG. 43 is a block diagram of a controllable release nasal systemincluding an external control portion;

FIG. 44 is a front cross-sectional view of an embodiment of acontrollable release nasal device;

FIG. 45 is an illustration of an embodiment of controllable releasenasal device including a delivery portion and a sensor;

FIG. 46 is an illustration of another embodiment of controllable releasenasal device including a delivery portion and a sensor;

FIG. 47 is an illustration of another embodiment of controllable releasenasal device including a delivery portion and a sensor;

FIG. 48 depicts an embodiment of an active portion including a heatingelement;

FIG. 49 depicts an embodiment of an active portion including a coolingelement;

FIG. 50 depicts an embodiment of an active portion including anelectromagnetic radiation source;

FIG. 51 depicts an embodiment of an active portion including an acousticsignal source;

FIG. 52 depicts an embodiment of an active portion including a negativepressure source;

FIG. 53 depicts an embodiment of an active portion including a positivepressure source;

FIG. 54 is an illustration of another embodiment of a controllablerelease nasal device;

FIG. 55 is a depiction of an embodiment of a controllable release nasaldevice including a material collection structure;

FIG. 56 is a flow diagram of a method of delivering a material to anasal region of a subject;

FIG. 57 is a flow diagram of a method of delivering a material to anasal region of a subject;

FIG. 58 is a flow diagram of a method of delivering a material to anasal region of a subject;

FIG. 59 is a flow diagram of a method of delivering a material to anasal region of a subject;

FIG. 60 is a flow diagram of a method of delivering a material to anasal region of a subject;

FIG. 61 is a flow diagram showing further aspects of a method ofdelivering a material to a nasal region of a subject;

FIG. 62 is a flow diagram showing further aspects of a method ofdelivering a material to a nasal region of a subject;

FIG. 63 is a flow diagram showing further aspects of a method ofdelivering a material to a nasal region of a subject;

FIG. 64 is a flow diagram showing further aspects of a method ofdelivering a material to a nasal region of a subject;

FIG. 65 is a flow diagram showing further aspects of a method ofdelivering a material to a nasal region of a subject; and

FIG. 66 is a schematic diagram of software for controlling release of amaterial from device mounted within a nasal region of a subject.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

FIG. 1 is a cross-sectional illustration of a head 10 of a person,showing the basic anatomy of nasal region 12. The mouth 14 and tongue 16are also indicated in FIG. 1. Nasal region 12 includes nostril 18 andnasal cavity 20. Nasopharynx 22 is the uppermost portion of the pharynx(throat) 24, which connects to esophagus 26. Nasopharynx 22 connects tonasal cavity 20 via internal naris 28. Trachea (windpipe) 30 liesanterior to esophagus 26. Epiglottis 32 closes off the opening of larynx34 leading to trachea 30 (shown with a solid line) during eating anddrinking, and opens (shown with a dashed line) to permit the flow of airbetween pharynx 24 and trachea 30 during breathing. Nasal conchae 36form shelf-like projections which may be seen more clearly in the frontcross-sectional view of FIG. 2. The olfactory region 38 is located inthe uppermost portion of nasal cavity 20. The nasal cavity 20 is dividedinto right side and left sides by nasal septum 40, as shown in FIG. 2.Nasal mucosa 42 lines the interior of the nasal cavity 20, as shown by agray line in FIG. 2. (The nasal mucosa will not be indicated in otherfigures, but may be expected to be present within the nasal cavity undernormal circumstances.)

In the example depicted in FIGS. 1 and 2, a delivery device 44 formingat least a portion of a controllable release nasal system is positionedwithin nostril 18 of nasal region 12. Delivery device 44 may be aself-expanding device that may be positioned within the nostril, forexample by a care provider or by the person using the delivery device,and then may expand intrinsically or be made to expand under control toprovide a snug fit sufficient to retain delivery device 40 within thenostril for as long as is desired.

FIG. 3 illustrates further aspects of delivery device 44. As shown inFIG. 3, in one aspect, an embodiment of a controllable release nasalsystem may include a structural element 50 including at least onepositioning portion 52 configured for contacting an interior surface 54of a nasal region (in this example, nostril 18) and mounting thestructural element 50 within the nasal region of a subject; a deliveryportion 56 mounted relative to the structural element 50 and configuredto release at least one material responsive to a delivery controlsignal; and control signal generation circuitry 58 configured togenerate a delivery control signal corresponding to a desired pattern ofrelease of the at least one material into the nasal region. In theexample of FIG. 3, positioning portion 52 is the exterior surface ofstructural element 50, which mounts structural element 50 within thenasal region (i.e., nostril 18 in this example) by a pressure and/orfrictional fit. In other embodiments, other types of positioningportions may be used, as will be discussed herein. Delivery device 44may include one or more sensor 62, which may be capable of detecting aphysiological or environmental condition. Control signal generationcircuitry 58 may receive as input a signal from sensor 62, which may beused in the calculation of the control signal for controlling therelease of material from delivery portion 56.

A delivery portion of a controllable release nasal system (for example,delivery portion 56 of delivery device 44 in FIG. 3) may be designed torelease material into different portions of the nasal region dependingon various considerations, including the specific material beingdelivered, the intended effect of the material, sensed ambientphysiological and/or environmental conditions, and, in someapplications, the mechanism of absorption or uptake of the material bythe body. In some embodiments, the material may be released directlyinto the nasal mucosa for absorption by local tissue Or by bloodcirculating through local fine capillaries, while in other embodiments,the material may be released into the nasal cavity in the form of aliquid, a gas, finely dispersed particles or droplets, or mixturesthereof, which may be carried by ambient airflow to more distantportions of the nasal mucosa or other portions of the respiratory tract,which may be exhaled along with exhaled gases, or which may be inhaledto various depths of the bronchial tree or within or into thegas-exchange portions of the lung, for example. In some embodiments, thefinely dispersed particles or droplets may be controlled to be withinthe diameter-range of 0.01 to 0.00001 cm, for example.

Materials delivered to the nasal regions may have a number of effects oruses. In some cases, materials such as odorants or neurotransmitters maystimulate the olfactory region to produce a sensory effect, for examplefor an esthetic, recreational, or medical purpose (e.g., aromatherapy;blockade, modification or enhancement of the flavors of foods, drinks,or orally delivered medications; one-or-more scents or olfactorymodulators delivered according to a pattern or script in order toprovide an olfactory analog to a soundtrack of a motion picture;amplified delivery of scents or odorants or olfactory modulators tosupplement deficiencies or enhance to supra-normal levels the innatesense of smell, etc.). In some embodiments, materials may be releasedfor delivery to the nasal mucosa and/or to sites elsewhere in therespiratory tract for absorption into the blood to effect systemicdelivery of the materials, which may be, for example, various types ofdrugs, medications, contraceptives, hormones, vaccines,tolerance-inducing allergens, or therapeutic compounds. In someembodiments, materials may be delivered to the nasal mucosa or elsewherein the respiratory tract to produce a local effect (e.g., to reduceinflammation or swelling of tissues, or for anti-pathogenic action) orinhaled into the lungs either to produce a local effect or for systemicuptake. In some embodiments, the material may form a functional coatingon the surface of the nasal region, respiratory tract portion or lung,rather than be absorbed, e.g. to function as a surfactant, a protectivelayer, or a barrier. In some embodiments, one or more materialsdelivered into the nasal region may act on exhaled gases to act on or incooperation with substances in the exhaled gases, for example to removeundesired materials from the exhaled gases, or to enhance, amplify ormodify the effect of substances of interest in the exhaled gases.

Some embodiments of controllable release nasal systems may be consideredto be lumenally active devices. Lumenally active devices in general aredescribed in commonly owned U.S. patent application Ser. No. 11/403,230,entitled “Lumenally Active Device” and filed Apr. 12, 2006, which isincorporated herein by reference.

In some aspects, as described herein, controllable release nasal systemsmay release materials into a body lumen (e.g., a nasal cavity ornostril), while in other aspects, controllable release nasal systems mayrelease materials into tissue surrounding the lumen and not into thelumen per se. The “Lumenally Active Device” patent application describesa lumenally active device which may include a structural elementconfigured to fit within at least a portion of a body lumen, thestructural element including a lumen-wall-engaging portion and afluid-contacting portion configured to contact fluid within the bodylumen; a sensor capable of detecting a condition of interest in thefluid; response initiation circuitry operatively connected to the sensorand configured to generate a response initiation signal upon detectionof the condition of interest in the fluid by the sensor; and an activeportion operatively connected to the response initiation circuitry andcapable of producing a response upon receipt of the response initiationsignal. Such a system is depicted in FIG. 4, which shows a deliverydevice 110 positioned in a body lumen 112. Body lumen 112 is defined bywall portions 114, which may be the walls of lumen-containing structurewithin the body of an organism, e.g., a nasal region or, in otherembodiments and applications, a blood vessel or other lumen containingstructure. Delivery device 110 includes structural element 116, sensor118, response initiation circuitry 120, and active portion 122. A fluidmay flow through lumen 112. The term fluid, as used herein, may refer toliquids, gases, and other compositions, mixtures, or materialsexhibiting fluid behavior. The fluid within the body lumen may include aliquid, or a gas or gaseous mixtures. As used herein, the term fluid mayencompass liquids, gases, or mixtures thereof that also include solidparticles in a fluid carrier. Liquids may include mixtures of two ormore different liquids, solutions, slurries, or suspensions. Examples ofliquids present within body lumens include blood, lymph, serum, urine,semen, digestive fluids, tears, saliva, mucus, cerebro-spinal fluid,intestinal contents, bile, epithelial exudate, or esophageal contents.Liquids present within body lumens may include synthetic or introducedliquids, such as blood substitutes or drug, nutrient, or (possiblybuffered) saline or electrolyte solutions. Fluids may include liquidscontaining dissolved gases or gas bubbles, or gases containing fineliquid droplets or solid particles. Gases or gaseous mixtures foundwithin body lumens may include inhaled and exhaled air, e.g. in thenasal or respiratory tract, or intestinal gases. According to thisdefinition, fluids within the nasal region will typically include gasesand mixtures of gases. Fluid may flow through the central openings 126of structural element 116, with the interior surface of structuralelement 116 forming fluid-contacting surface 128. In the embodiment ofFIG. 4, sensor 118 and active portion 122 may be located at afluid-contacting surface 128. Outer surface 130 of structural element116 may function as a lumen-wall engaging portion, providing africtional fit with wall portions 114. In other embodiments of deliverydevices, other structures and methods for engaging the lumen wall may beemployed. Structural elements may include two or more openings or lumenspassing through the structural element, rather than a single centralopening as depicted in FIG. 4, and the lumen-wall-engaging portion ofthe structural element is not limited to embodiments having asubstantially smooth outer surface that conforms to the interiorcross-section of a nasal lumen, but may have a variety of surfaceshapes, textures, and contours, some of which may conform or contactonly a portion or portions of the interior cross section of a nasallumen.

Embodiments of the lumenally-active system may be configured for use invarious different body lumens of an organism including, for example, anostril or nasal cavity, one or more portions of the respiratory tract,the cardiovascular system (e.g., a blood vessel), the lymphatic system,the biliary tract, the urogenital tract, the oral cavity, the digestivetract, the tear ducts, a glandular system, a reproductive tract orportion thereof, the cerebral ventricles, spinal canal, and otherfluid-containing structure of the nervous system of an organism. Otherfluid-containing lumens within the body may be found in the auditory orvisual systems, or in interconnections thereof, e.g., the Eustachiantubes.

Wherever a controllable release nasal system is to be used, thedimensions and mechanical properties (e.g., rigidity) of the deliverydevice, and particularly of the structural element of the deliverydevice, may be selected for compatibility with the location of use, inorder to provide for reliable positioning of the device and to preventdamage to the lumen-containing structure.

The structural element may include a self-expanding structure configuredto expand to mount the structural element within the nasal region of thesubject. For example, structural element 50 of the delivery devicedepicted in FIGS. 1 through 3 is a generally spring-like structure thatmay be formed of a loop of resilient, springy, or self-expandingmaterial which may be compressed slightly by virtue of slit 60, as shownin FIG. 3, to permit insertion into the nostril and which may thenexpand sufficiently to cause the structural element to be retainedwithin the nostril until it is to be removed. In such embodiments, theresilient, springy or self-expanding portion of the structural elementmay function as the positioning portion of the delivery device.

FIGS. 5 through 7 depict a further spring-like structural element whichmay be placed between the nasal conchae and which may expand slightly tosecure it in place. FIG. 5 depicts structural element 150. Structuralelement 150 includes end regions 152, curved portion 154, inner surface156 and outer surface 158. Structural element 150 may also include adelivery portion and control signal generation circuitry (not shown).Structural element 150 may be compressed by pressing together endregions 152. As shown in FIG. 6, structural element 150 may be insertedbetween two nasal conchae 36, and allowed to expand to hold it in place.The position of structural element 150 relative to nostrils 18, nasalseptum 40, and nasal conchae 36, can be seen in both FIG. 6 and FIG. 7.

The self-expanding structure may permit the structural element to beplaced within a nasal region (e.g., a nostril, or a portion of a nasalcavity) while in a first, contracted, state and then transformed into asecond, expanded, state of a nature such that the structural elementcontacts opposing interior walls of a portion of the nasal region inorder to satisfactorily position and mount the structural element atleast temporarily within the nasal region.

In some embodiments, as depicted in FIGS. 8 and 9, a structural element160 may include a clip structure 162, at least a portion of which isconfigured to extend outside the nasal region of the subject. In FIG. 8,clip structure 162 clamps onto nasal septum 40, with a portionprojecting into a first nostril 18 a, with structural element 160residing within second nostril 18 b. Construction of clip structures ofthis general type may be as described, for example, in U.S. Pat. No.5,947,119, which is incorporated herein by reference. In the embodimentshown in FIG. 8, a single structural element 160 is shown. In otherembodiments (not shown), a clip structure may have associated with ittwo or more structural elements, with one residing in each nostril. Instill other embodiments, two or more structural elements may reside inan individual nostril, or in both nostrils. FIG. 9 is a side view ofstructural element 160 with clip structure 162.

In some embodiments, a controllable release nasal system may beconfigured to reside entirely within the nasal region of the subject. Inother embodiments of a controllable release nasal system, a firstportion of the controllable release nasal system may be configured toreside within the nasal region of the subject and a second portion ofthe controllable release nasa system may be configured to resideexternal to the nasal region of the subject. The second portion may besimply structural, like the extra-nasal portion depicted in FIG. 8.However, in some embodiments, the second portion of the controllablerelease nasal system may include components such as the control signalgeneration circuitry or a source of the material delivered by the device(or a component thereof).

FIGS. 10 and 11 depict an embodiment of a structural element 180 inwhich the positioning portion may include an adhesive 182. As shown inthe front sectional view of FIG. 10, structural element 180 is locatedin nasal cavity 20 and positioned against nasal septum 40 with a layerof adhesive 182. The side sectional view of FIG. 11 illustrates theposition of structural element 180 within nasal cavity 20. In otherembodiments, the positioning portion may include a remotely guidablesection and/or a means for facilitating extraction when it is desired toremove the structural element or device from the nasal region. In someembodiments, the positioning portion may include other structures formounting or positioning the structural element within at least a part ofa nasal region. The positioning portion may include one or morebarb-like structures (e.g., as depicted in FIG. 21), at least onevacuum-generating device capable of mounting the structural elementwithin a nasal region by producing sufficient vacuum (or suction) tocause the structural element to stick to at least a portion of the nasalregion, or at least one hair-engaging structure (which may be, forexample, a clip, clasp, grip or coil-like structure capable ofreversibly engaging one or more hairs within the nasal region to mountthe structural element within the nasal region).

In the various embodiments disclosed herein, the positioning portion maybe used to mount the structural element of the delivery device within anasal region for a use period that may be brief (e.g. on the order ofminutes) or extended (weeks, months, or longer). Following placement ofthe structural element in the desired location for use, which may bedone manually or with the use of an insertion device, the deliverydevice may be held in place without further intervention. Thepositioning portion may include any fastening structure or mechanismthat is capable of mounting (securing, retaining and/or supporting) thestructural element within the nasal region for the duration of its usewithout the need for the person using the device (or another party) tohold or otherwise maintain the structural element in place.

As shown variously in FIGS. 1 through 11, in some embodiments, at leasta part of the structural element may be configured for mounting within anostril of the subject, and in some embodiments at least a part of thestructural element may be configured for mounting within a nasal cavityof the subject.

FIGS. 12 through 15 depict a number of possible configurations forstructural elements of delivery devices for use in body lumens.Structural elements may have the form of a short cylinder 250, as shownin FIG. 12; an annulus 252, as shown in FIG. 13; a cylinder 254, asshown in FIG. 14; or a spiral 256, as shown in FIG. 15. Elongated formssuch as cylinder 254 or spiral 256 may be suitable for use in generallytubular portions of lumen-containing structures such as the nostrils,possibly with a significant taper over their length (not shown in FIGS.14-15). Structural elements may be formed from various materials,including metals, polymers, fabrics, and various composite materials,including ones of either inorganic or organic character, the latterincluding materials of both biologic and abiologic origin, selected toprovide suitable biocompatibility and mechanical properties.

As shown in FIGS. 16-18, the basic form of a structural element may besubject to different variations, e.g., by perforations, as shown instructural element 260 in FIG. 16; a mesh structure, as shown instructural element 262 in FIG. 16; or the inclusion of one or more slots264 in structural element 266 in FIG. 18. Slot 264 runs along the entirelength of structural element 266; in other embodiments, one or moreslots (or mesh or perforations) may be present in only a portion of thestructural element. By using spiral, mesh, or slotted structuralelements (as in FIGS. 15, 17, and 18) formed from resilient, elastic,springy or self-expanding/self-contracting materials or substrates,suitable structural elements may be formed. Spiral, mesh, or slottedelements need not be elongated tubular structures as depicted in FIGS.15, 17, and 18, but may be shorter, generally ring-like structuressimilar in profile to the structural element shown in FIGS. 1 through 3,which is essentially a spring having only a single loop.

A self-expanding or contracting structural element may facilitatepositioning or secure emplacement of the structural element within abody lumen of an organism, such as a nasal structure. In someembodiments, flexible material having adjustable diameter, taper, andlength properties may be used. For example, some materials may changefrom a longer, narrower configuration 270 as shown in FIG. 19A, to ashorter, wider configuration 272 as shown in FIG. 19B, or may taper overtheir length. Structural elements that may exhibit this type ofexpansion/contraction property may include mesh structures formed ofvarious metals or plastics, and some polymeric materials, for example.

The exemplary embodiments depicted in FIGS. 1-4 and 12-19B either aresubstantially cylindrical, and hollow and tubular in configuration, orring-like, with a single central opening. Thus, the exterior of thecylindrical or ring-like structural element may contact and engage thewall of the body lumen, and the interior of the structural element(within the single central opening) may form a fluid-contacting portionof the structural element. Structural elements are not limited tocylindrical or ring-like structural elements having a single centralopening, however.

FIGS. 20 through 25 depict a variety of cross-sectional configurationsfor structural elements of delivery devices. Note that the illustratedcross-sectional configurations are suitable to be fit into a lumenhaving a roughly circular cross-section, as would be the case, forexample, with a nostril viewed from above or below. Analogous structuresmay be designed to fit within lumens having non-circular cross-sections.In FIG. 20, a delivery device 300 is positioned in lumen 302 oflumen-containing structure 304. In this embodiment, fluid-contactingportion 306 may be the surface of structural element 300 that faceslumen 302, while the lumen-wall engaging portion 308 may be a layer oftissue adhesive on surface 310 of structural element 300. An example ofa device having a cross-section similar to that shown in FIG. 20, is theembodiment shown in FIGS. 10 and 11.

FIG. 21 depicts in cross-section a further embodiment of a structuralelement 350 in lumen 352 of lumen-containing structure 354. Structuralelement 350 includes multiple openings 356, each of which includes aninterior surface 358 that forms a fluid-contacting portion. Structuralelement 350 may include one or more barb-like structures 360 that serveas lumen-wall engaging portions that maintain structural element 350 inposition with respect to lumen-containing structure 354. Barb likestructures may be fixed in some embodiments, or retractable or moveablein other embodiments.

FIG. 22 depicts in cross-section an embodiment of a structural element400 in lumen 402 of lumen-containing structure 404. Structural element400 includes a large central opening 406 and multiple surroundingopenings 408. The interior surface of each opening 406 or 408 serves asa fluid-contacting portion, while projections 410 function as lumen-wallengaging portions, which may engage frictionally or may project slightlyinto the interior of the wall of lumen-containing structure 404.

FIG. 23 depicts a further embodiment in which structural element 450 hasa substantially oval cross-section and includes a slot 452.Lumen-containing structure 454 may be generally oval in cross section,or may be flexible enough to be deformed to the shape of structuralelement 450. Structural element 450 may be a compressed spring-likestructure that produces outward forces as indicated by the black arrows,so that end portions 456 of structural element 450 thus press againstand engage the lumen wall. Interior surface 458 of structural element450 serves as the fluid-contacting portion of structural element 450.

FIG. 24 is a cross-sectional view of a structural element 500 in alumen-containing structure 502. Structural element 500 includes multipleprojecting arms 504 which contact lumen wall 506 of lumen-containingstructure 502, and function as lumen-wall engaging portions. Innersurfaces 508 of arms 504 function as fluid-contacting portions ofstructural element 500.

FIG. 25 depicts (in cross-section) another example of a structuralelement 550 positioned within a lumen-containing structure 552.Structural element 550 includes two openings 554. The interior surfaces556 of openings 554 function as fluid-contacting portions, while theouter surface 558 of structural element 550 serves as a lumen-wallengaging portion.

The structural elements depicted in FIGS. 1-25 are intended to serve asexamples, and are in no way limiting. The choice of structural elementsize and configuration appropriate for a particular body lumen may beselected by a person of skill in the art. Structural elements may beconstructed by a variety of manufacturing methods, from a variety ofmaterials. Appropriate materials may include metals, ceramics, polymers,and composite materials having suitable biocompatibility,sterilizability, mechanical, and physical properties, as will be knownto those of skill in the art. Examples of materials and selectioncriteria are described, for example, in The Biomedical EngineeringHandbook, Second Edition, Volume I, J. D. Bronzino, Ed., Copyright 2000,CRC Press LLC, pp. IV-1-43-31. Manufacturing techniques may includeinjection molding, extrusion, die-cutting, rapid-prototyping, orself-assembly, for example, and will depend on the choice of materialand device size and configuration. Sensing and active portions of thedelivery device as well as associated electrical circuitry may befabricated on the structural element using various microfabricationand/or MEMS techniques, or may be constructed separately andsubsequently assembled to the structural element, as one or moredistinct components.

In a controllable release nasal device or system, a fluid contactingportion typically contacts inspired or expired air/gases moving throughthe nasal region, while a lumen wall engaging portion may contact thetissue lining the wall of the nostril or the nasal cavity. In someembodiments, the lumen wall-engaging portion may closely contact thenasal mucosa, and/or may be in proximity to capillary beds in the nasalmucosa. In some embodiments of a controllable release nasal device orsystem, a lumen wall engaging portion may be in proximity to neuraltissue in the olfactory region. Contact with or proximity to mucosa,capillaries, and/or neural tissue by the lumen wall engaging portion ofa controllable release nasal device or system may facilitate the releaseor transfer of material to some or all of these tissues by a deliveryportion located on the lumen wall engaging portion, or the sensing ofvarious parameters regarding or pertinent to these tissues by a sensingportion. Similarly, contact or proximity of a fluid-contacting portionof a controllable release nasal device or system to a fluid mixture(i.e., gases, fine particles, liquid droplets, etc.) within the nostrilsor nasal cavity may facilitate the release of materials into the fluidmixture by a delivery portion located on the fluid-contacting portion,or the sensing of various parameters pertinent to the fluid mixture by asensing function.

The delivery portion may be configured to release the at least onematerial directly into the nasal mucosa for absorption in someembodiment, as illustrated in FIG. 26. Structural element 600, which issimilar to that depicted in FIGS. 10 and 11, may be positioned againstnasal mucosa 602 on the surface of nasal septum 40, so that deliveryportion 604 is positioned adjacent to nasal mucosa 602. Material 606released from delivery portion 604 may then be absorbed into nasalmucosa 602. Control signal generation circuitry 608 on structuralelement 600 may generate a control signal that stimulates release ofmaterial 606 from delivery portion 604. In some such embodiments, thedelivery portion may include a permeation enhancer (that may be releasedin association with the material being delivered, for example) that iscapable of increasing the permeation of the at least one material intothe nasal mucosa. Permeation enhancers may include chemical permeationenhancers such as isopropyl myristate, bile salts, surfactants, fattyacids and derivatives, chelators, cyclodextrins or chitosan, asdescribed in Murthy, S. N. Hiremath, S. R. R. “Physical and ChemicalPermeation Enhancers in Transdermal Deliver) of Terbutaline Sulphate, ”AAPS PharmSciTech., 2001, 2(1) or Senel, S. Hincal, A. A. “Drugpermeation enhancement via buccal route: possibilities and limitations,” J. Control Release, 2001 May 14, 72(1-3):133-44, both of which areincorporated herein by reference. Permeation may also be enhanced byincluding a magnetic component, as described in Murthy, S. N., Hiremath,S. R. R. “Physical and Chemical Permeation Enhancers in TransdermalDelivery of Terbutaline Sulphate, ” AAPS PharmSciTech., 2001, 2(1), orby the use of microprotrusions of the type described in U.S. Pat. No.6,953,589, or other microneedles or microfine lances. The foregoingreferences are incorporated herein by reference. Other technologies thatmay used for enhancing permeability of materials include, but are notlimited to, iontophoresis, microdialysis, ultrafiltration,electromagnetic, osmotic, electroosmosis, sonophoresis, microdialysis,suction, electroporation, thermal poration, microporation, microfinecannulas, skin permeabilization, or a laser.

As illustrated in FIG. 27, in other embodiments, the delivery portionmay be configured to release the at least one material into the nasalcavity in the form of a spray or similar aero-suspension of finelydispersed particles, powders or droplets. In FIG. 27, delivery device620 includes structural element 622 similar to structural element 160 inFIGS. 8 and 9. Delivery portion 624 of delivery device 620 is configuredto direct the release of the at least one material 626 toward the nasalmucosa, e.g. in the interior of nasal cavity 20. In other embodiments,as shown in FIG. 28, delivery device 650 may include delivery portion652 configured to direct the release of the at least one material 654toward the olfactory portion 656 of the nasal mucosa. In still otherembodiments, as shown in FIG. 29, a delivery device 670 may include adelivery portion 672 configured to direct the release of the at leastone material 674 toward the nasopharynx 22. Material directed towardnasopharynx may subsequently be inhaled into the other portions of therespiratory tract, including the lungs, of the person in which deliverydevice 670 is emplaced, and it may be configured for preferentialdelivery to or deposition onto one or more surfaces of particularportions thereof.

In other embodiments, the active portion of a delivery device mayinclude a material release structure operatively coupled to the responseinitiation circuitry and configured to release a material in response todetection of a condition of interest. A condition of interest may bedetected by a sensor, which may be located in or on the release deliverydevice.

FIG. 30 depicts a delivery device 700 including a structural element702, sensor 704, control signal generation circuitry 706, and releasestructure 708 including release mechanism 710. Structural element 702includes external surface 712, configured to fit within a body lumen,and internal surface 714 defining central opening 716, through which afluid may flow. Upon sensing of a condition of interest in the fluid bysensor 704, control signal generation circuitry 706 may cause release ofmaterial from material release structure 708 by activating releasemechanism 710. Release mechanism 710 may include a variety of differenttypes of release mechanisms, including, for example a controllable valveas depicted in FIG.30. Various types of valves and microvalves are knownto those of skill in the art, and may be used to regulate the release ofmaterial from material release structure 708 in response to a controlsignal from control signal generation circuitry 706. Control signalgeneration circuitry 706 may activate release mechanism 710 by supplyinga delivery control signal, which may be an electrical signal, forexample. In some embodiments, other types of delivery control signals,including magnetic signals, optical signals, acoustic signals, or othertypes of signals may be used. Combinations of several types of signalsmay be used in some embodiments. In some embodiments, control signalgeneration circuitry 706 may cause release of material from materialrelease structure in response to passage of a certain amount of time, asmonitored, for example, by a timekeeping device. In some embodiments,material release structure 708 may include a pressurized reservoir ofmaterial. In still other embodiments, the material (or materials) to bereleased may be generated within the material release structure. Inother embodiments, the material(s) may diffuse away from the releasestructure along a concentration gradient.

In some embodiments, the system may include an extension connected tothe structural element, wherein the structural element is mounted with afirst portion of the nasal region of the subject, and wherein theextension extends from the structural element to a second portion of thenasal region to deliver the at least one material to the second portionof the nasal region. FIG. 31 illustrates an embodiment of a deliverydevice including a structural element 720 mounted in a nostril 18 of aperson 11 by means of clip 722. Structural element 720 also includesextension 724 that project toward a more internal portion of the nasalregion, which in this example is olfactory mucosa 38, where it releasesmaterial from end portion 726. End portion 726 may be the opening of atubular structure connected to a material source in structural element720, or end portion 726 may be a release location for a material sourcelocated at end portion 726. Other embodiments of delivery devices mayinclude extensions configured to deliver material(s) to other portionsof the nasal region, while the main part of the delivery device residesin a relatively accessible location, for example, the nostril.

FIG. 32 illustrates, in cross sectional view, a structural element 750of a delivery device positioned in a lumen-containing structure 752. Areservoir 754 contains stored deliverable material. Barrier 756 is acontrollable barrier that controls the release of the stored deliverablematerial into central opening 758, and thus into a fluid that fillsand/or flows through lumen-containing structure 752. Various types ofbarriers may be used to control the release of material from thedelivery portion of the controllable release nasal system. For example,the delivery portion may include a rupturable barrier, a barrier havinga controllable permeability, a stimulus-responsive gel or polymer, or apressurized fluid source.

FIG. 33 illustrates an embodiment including a structural element 800 ofa delivery device positioned in a lumen-containing structure 802. Tworeservoirs 804 contain stored deliverable material(s). Each reservoir804 includes a controllable barrier 806 that controls release of the atleast one stored deliverable material. In the embodiment of FIG. 33,activation of barrier 806 causes release of the at least one storeddeliverable material toward the lumen wall of lumen-containing structure802, rather than into central opening 808. FIG. 33 also illustrates thatdelivery devices may include more than one reservoir.

FIGS. 34A, 34B, 35A, 35B, 36A and 36B, illustrate several alternativeembodiments of material release structures that include controllablebarriers. In FIGS. 34A and 34B, release structure 850 includes reservoir852 containing stored deliverable material 854. As shown in FIG. 34A,while rupturable barrier 856 is intact, stored deliverable material 854is contained within reservoir 852. As shown in FIG. 34B, when rupturablebarrier 856 has been ruptured (as indicated by reference number 856′),deliverable material 854 may be released from reservoir 852. Rupturablebarrier 856 may be ruptured by an increase of pressure in reservoir 852caused by heating, for example, which may be controlled by responseinitiation circuitry. In another alternative shown in FIGS. 35A and 35B,release structure 900 includes reservoir 902 containing storeddeliverable material 904. As shown in FIG. 35A, while degradable barrier906 is intact, stored deliverable material 904 is contained withinreservoir 902. As shown in FIG. 35B, degradation of degradable barrier906 to degraded form 906′ causes stored deliverable material 904 to bereleased from reservoir 902. FIGS. 36A and 36B depict release structure950 including reservoir 952 containing stored deliverable material 954.FIG. 36A, shows barrier 956, which has a controllable permeability, in afirst, impermeable state, while FIG. 36B shows barrier 956 in a second,permeable state (indicated by reference number 956′). Stored deliverablematerial 954 passes through barrier 956′, when it is in its permeablestate, and is released. Rupturable barriers as described above may beformed from a variety of materials, including, but not limited to,metals, polymers, crystalline materials, glasses, ceramics,semiconductors, etc. Release of materials through rupture or degradationof a barrier is also described in U.S. Pat. No. 6,773,429, which isincorporated herein by reference. Semipermable barriers having variablepermeability are described, for example, in U.S. Pat. No. 6,669,683,which is incorporated herein by reference. Those of skill in the artwill appreciate that barriers can be formed and operated reversiblythrough multiple release cycles, in addition to the single-releasefunctionality available from a rupturable barrier.

In some embodiments, a delivery device may include one or more storeddeliverable materials dispersed in a carrier material. Storeddeliverable material may be released from the carrier material by arelease mechanism upon activation of the release mechanism. The releaseddeliverable material may be released into a central opening of adelivery device and/or into the body lumen. FIGS. 37A and 37B depict ingreater detail the release of stored deliverable material from thecarrier material. In FIG. 37A, deliverable material 1024 is stored incarrier material 1026. Carrier material 1026 may be, for example, apolymeric material such as a hydrogel, and deliverable material isdispersed or dissolved within carrier material 1026. Release mechanism1028 may be a heating element, for example a resistive element connecteddirectly to response initiation circuitry, or an electrically ormagnetically responsive material that may be caused to move, vibrate,heat, by an externally applied electromagnetic field, which in turncauses release of deliverable material 1024 from carrier material 1026,as shown in FIG. 29B. See, for example, U.S. Pat. Nos. 5,019,372 and5,830,207, which are incorporated herein by reference. In someembodiments, an electrically Or magnetically active component may beheatable by an electromagnetic control signal, and heating of theelectrically or magnetically active component may cause the polymer toundergo a change in configuration. An example of a magneticallyresponsive polymer is described, for example, in Neto, et al, “Optical,Magnetic and Dielectric Properties of Non-Liquid Crystalline ElastomersDoped with Magnetic Colloids”; Brazilian Journal of Physics; bearing adate of Mar. 2005; pp. 184-189; Volume 35, Number 1, which isincorporated herein by reference. Other exemplary materials andstructures are described in Agarwal et al., “Magnetically-driventemperature-controlled microfluidic actuators”; pp. 1-5; located at:http://www.unl.im.dendai.ac.jp/INSS2004/INSS2004_papers/OralPresentations/C2.pdf or U.S. Pat. No. 6,607,553, each of which is incorporated herein byreference. Other examples of stimulus-responsive gels or polymers aresubstance-responsive gels or polymers that swell, change shape, etc. inresponse to a change in pH, glucose, or other substance (as selected byembedded antibodies, for example). Examples of stimulus responsive gelsor polymers are described in Langer, R. & Peppas, N., “Advances inBiomaterials, Drug Delivery, and Bionanotechnology,” AIChE Journal,December. 2003, Vol. 49, No. 12, pp. 2990-3006, which is incorporatedherein by reference.

The controllable release nasal system may include a source of thematerial located in or on the structural element, as depicted generallyin FIGS. 30-36B (e.g., either as a reservoir containing the material asshown in FIGS. 34A-36B, or as a portion of carrier material containing adispersed or dissolved material, as shown in FIGS. 37A and 37B .Alternatively, a controllable release nasal system may include a sourceof material located external to the nasal region of the subject andconnected to the delivery portion via a delivery tube that enters thenasal region of the subject via a nostril of the subject, as shown inFIG. 38

In FIG. 38, structural element 1050 includes a clip-like structure thatfits onto nasal septum 40, with end regions 1052 projecting into atleast one nostril 18, which end-regions may include at-least-one sensor(not shown). Material to be delivered may be supplied from supplyreservoir 1054 via supply tube 1056. A control device 1058 includingcontrol signal generation circuitry 1059 may control the flow ofmaterial (e.g., a gas or gaseous mixture, possibly carrying fluiddroplets or fine solid particles) from supply reservoir 1054 to supplytube 1056 and thence into nostrils 18. Supply reservoir 1054 may be atank capable of containing the material in liquid or gaseous form, or itmay contain a solid source which releases material upon heating, changein pressure, or a chemical reaction, for example. In some embodiments, acarrier gas or liquid may be stored in supply reservoir 1054, and one ormore active component of the material may be added from a secondarysource that may be regulated by control device 1058, for example.

FIG. 39 is a detailed cross-sectional view of structural element 1050 ofthe embodiment shown in FIG. 38. Supply tube 1056 fits over stem portion1060 of structural element 1050. Channel 1062 in supply tube 1056 alignswith channel 1064 in structural element 1050. Channel 1064 connects tobranch channels 1066 and 1068, which lead to openings 1070 and 1072,respectively. Material may be delivered to the one-or-both nostrils viaopenings 1070 and 1072. Structural element 1050 also includes sensors1074 and 1076, which are connected to leads 1078 and 1080, respectively.Leads 1078 and 1080 are connected to leads 1082 and 1084, respectivelyin supply tube 1056 via contacts 1086 and 1088 in structural element1050 and corresponding contacts 1090 and 1092 in supply tube 1056. Leads1082 and 1084 connect sensors 1074 and 1076 to control signal generationcircuitry ( e.g., control signal generation circuitry 1059 as shown inFIG. 38), where they may serve to provide feedback signals which may beused in the determination of a delivery control signal for controllingthe delivery of the material. Sensors 1074 and 1076 may be any ofvarious types of sensors, as are known to those of skill in the art, forexample, gas sensors, temperature sensors, flow sensors, pressuresensors, moistur sensors, straing sensors, acoustic sensors,chemical-composition or -concentration sensors, or other types ofsensors as described elsewhere herein. Sensors 1074 and 1076 may bepositioned on structural element 1050 in such a manner that they contactthe nasal wall or septum, to sense a parameter of the nasal tissue, orthey may be positioned on structural element 1050 in such a way thatthey sense a parameter from a fluid (gas and/or liquid) within thenostril or nasal cavity.

The delivery portion of the controllable release nasal device or systemmay deliver a material to a nasal region or a portion thereof bydiffusion or low-speed dispersion of the material from the deliveryportion (e.g., as depicted in FIG. 26) or it may deliver the material ina spray or jet, as depicted in FIGS. 27 through 29. In some embodiments,the system may rely upon fluid (air/liquid) movement or pressure changesassociated with breathing activity to move or distribute the deliveredmaterial to the intended destination(s). FIG. 26 provides an example ofan embodiment that relies upon diffusion or dispersion of the materialinto tissue. FIGS. 27 through 29 and 38 depict examples of embodimentsin which the material may be delivered under pressure. For example,supply reservoir 1054 may be a pressurized tank. In other embodiments,the material may not be stored under pressure, but may have its pressureor speed-of-movement increased at the time of delivery by heating, forexample.

FIG. 40 is a schematic diagram of a controllable release nasal system1100 as described generally herein. Controllable release nasal system1100 may include some or all of structural element 1102, positioningportion 1104, control signal generation circuitry 1106, delivery portion1108, material source 1110, and power source 1112, as well as a sensingfunction (not shown explicitly).

FIG. 41 is a block diagram illustrating in greater detail variouscircuitry components of a controllable release nasal system. Circuitrycomponents may include electrical circuitry components, or,alternatively or in addition, fluid circuitry, optical circuitry,biological or chemical circuitry, chemo-mechanical circuitry, and/orother types of circuitry in which information is carried, transmitted,and/or manipulated by non-electronic means. The controllable releasenasal system may include one or more sensors 1150 for measuring ordetecting a condition of interest. Sensing circuitry 1152 may beassociated with sensors 1150. The controllable release nasal system mayinclude various control circuitry 1154, including control signalgeneration circuitry 1156. Control signal generation circuitry 1156provides a delivery control signal to delivery portion 1158. Deliveryportion may receive a material to be delivered from material source1160. Control circuitry 1154 may also include data storage portion 1162,which may, for example, be used to store pattern data 1164 or patternparameters 1166. Data storage portion 1162 may also be used to storesense data 1168 and/or sense parameters 1170, which may be derived froma sense signal, e.g. by sensing circuitry 1152. Control electronics mayinclude data transmission/reception circuitry 1172, which provides forthe transmission and reception of data and/or power signals between thedelivery device and remote circuitry 1174. User interface circuitry 1176may receive input signals from user input device 1178. User input device1178 may provide for the input of user instruction, parameter, etc. tocontrol circuitry 1154. Finally, one or more power sources 180 mayprovide power to circuitry and other components of the controllablerelease nasal system.

The control signal generation circuitry, and control circuitry ingeneral, may include a microprocessor and/or at least one of hardware,software, and firmware. The control signal generation circuitry may beconfigured to generate a delivery control signal based upon apre-determined delivery pattern, in which case the system may alsoinclude a memory location for storing the pre-determined deliverypattern (e.g., pattern data 1164 stored in data storage portion 1162).In some embodiments, the control signal generation circuitry may beconfigured to calculate a delivery control signal based upon one or morestored parameters. Again, the system may include a memory location forstoring the one or more parameters (e.g., pattern parameters 1166 orsense parameters 1170 stored in data storage portion 1162). For example,the control signal generation circuitry may be configured to generate adelivery control signal corresponding to a pattern of delivery of the atleast one material expected to produce a therapeutic effect or a sensoryeffect. In some embodiments, the control signal generation circuitry maybe configured to generate a delivery control signal corresponding to apattern of delivery of the at least one material expected to produce atherapeutic effect tailored specifically to the subject. For example,the control signal generation circuitry may be configured to generate adelivery control signal taking into account parameters such as the size,weight, gender, age, as well as specifics relating to the subject'spreferences, medical condition or other parameters.

Circuitry components as discussed in connection with FIG. 41 may belocated entirely on the structural element of a delivery device portionof a controllable release nasal system, or may be distributed betweenthe delivery device and a remote portion as depicted in FIG. 42. In FIG.42, a delivery device 1200 is positioned in nasal region 12 of head 10of a person 11. Remote portion 1102 may be held by person 11, orotherwise positioned nearby person 11. For example, remote portion 1202may be carried or attached to a wristband or necklace. Remote portion1102 may transmit signal 1204 to delivery device 1200. Signal 1204 maybe a one- or two-way signal, containing control, data, or power signals.In some embodiments, remote portion 1202 may permit person 11 to provideuser input to specify delivery of material to nasal region 12 withdelivery device 1200.

Alternatively, in some embodiments, control signal generation circuitrymay be located remote from the structural element and associated with atransmitting structure capable of transmitting the delivery controlsignal to the structural element, and wherein the delivery portion isassociated with a receiving structure capable of receiving the deliverycontrol signal. FIG. 43 is a block diagram of a controllable releasenasal system including a delivery device 1220 and remote portion 1222.Delivery device 1220 may include various components as depicted in FIG.41, including (but not limited to) control circuitry 1224, deliveryportion 1226, and one or both of a power receiver 1228 and datareceiver/transmitter 1230. In some embodiments, datareceiver/transmitter 1230 may only receive data signals, while in otherembodiments it may only transmit data signals, and in still otherembodiments it may both transmit and receive data signals. Powerreceiver 1228 may receive power signals transmitted from remote portion1222. Remote portion 1222 may include one or both of power source 1232and control signal generator 1234. Power transmitter 1236 may be used inconnection with power source 1232 in order to transmit power to powerreceiver 1228 in delivery device 1220. Data transmitter/receiver 1238may transmit a delivery control signal from control signal generator1234 to delivery device 1220, or receive sense or parameter data signalstransmitted from delivery device 1220 by data receiver/transmitter 1230.In some embodiments of the system, the control signal generationcircuitry may be a part of the delivery device, located in or on thestructural element.

In some embodiments of delivery devices or systems, a delivery devicemay be a self-contained device that may be positioned in a body lumenand that includes all functionalities necessary for operation of thedevice. In other embodiments, as shown in FIGS. 42 and 43, acontrollable release nasal system may include a delivery device that maybe placed in a nasal region, and a remote portion that includes aportion of the functionalities of the controllable release nasal system.In some embodiments, all functionalities essential for the operation ofthe delivery device may be located on the delivery device, but certainauxiliary functions may be located in the remote portion. For example,the remote portion may provide for monitoring of the operation of thedelivery device or data collection or analysis. The remote portion maybe located within the body of the subject at a distance from thedelivery device, or outside the body of the subject, as depicted in FIG.42, either proximate to or distant from it. Data and/or power signalsmay be transmitted between delivery device and remote portion with theuse of electromagnetic or acoustic signals, or, in some embodiments, maybe carried over electrical or optical links. In general, the remoteportion may be placed in a location where there is more space availablethan within the body lumen, that is more readily accessible, and soforth. It is contemplated that a portion of the circuitry portion of thecontrollable release nasal system (which may include hardware, firmware,software, or any combination thereof) may be located in a remoteportion. Methods of distributing functionalities of a system betweenhardware, firmware, and software located at two or more sites are wellknown to those of skill in the art. The control circuitry portion of thecontrollable release nasal system may include, but is not limited to,electrical circuitry associated with the sensor, response initiationcircuitry, and electronics associated with the active portion.

In various embodiments, the system may include a power source such as abattery. A power source may also be considered to include a powerreceiver capable of receiving inductively coupled power from an externalpower source, e.g., as depicted in FIG. 43. Delivery devices and systemsaccording to various embodiments as described herein may include a powersource, such as one or more batteries located on the delivery device,possibly a microbattery like those available from Quallion LLC(http://www.quallion.com) or designed as a film (U.S. Pat. Nos.5,338,625 and 5,705,293), which are incorporated herein by reference.Batteries may include primary or secondary batteries, including varioustypes of electrochemical energy storage devices. In some embodiments,the power source may be one or more fuel cell such as an enzymatic,microbial, or photosynthetic fuel cell or other biofuel cell(US20030152823A1; WO03106966A2, and “A Miniature Biofuel cell”; Chen, T.et al., J. Am. Chem. Soc., Vol. 123, pp. 8630-8631, 2001, all of whichare incorporated herein by reference), and could be of any size,including the micro- or nano-scale. In some embodiments, the powersource may be a nuclear battery. The power source may be any of variousmechanical energy storage devices, including but not limited topressurized bladders or reservoirs, wind-up and spring-loaded devices.The power source may be an energy-scavenging device such as apressure-rectifying mechanism that utilizes pulsatile changes in bloodpressure, for example, or an acceleration-rectifying mechanism as usedin self-winding watches; it may derive energy from the cyclic flow ofgas through the upper airway. In some embodiments, the power source maybe an electrical power source located remote from the structural elementand connected to the structural element by a wire, or an optical powersource located remote from the structural element and connected to thestructural element by a fiber-optic line or cable. In some embodiments,the power source may be a power receiver capable of receiving power froman external source, acoustic energy from an external source, a powerreceiver capable of receiving electromagnetic energy (e.g., microwave,infrared or optical electromagnetic energy) from an external source.

The control signal generation circuitry may include at least one ofhardware, software, and firmware; in some embodiments the control signalgeneration circuitry may include a microprocessor or a (programmable)logic array. The control signal generation circuitry may be located inor on the structural element in some embodiments, while in otherembodiments the response initiation circuitry may be at a locationremote from the structural element.

FIG. 44 depicts a controllable release nasal device 1300 including asensor 1302 capable of detecting a parameter of interest in the nasalregion of the subject. Controllable release nasal device 1300, mayinclude sensor 1302, control signal generation circuitry 1304, anddelivery portion 1306. The control signal generation circuitry may beconfigured to modulate generation of the delivery control signal basedupon at least one parameter of interest sensed by the sensor.Controllable release nasal device may be positioned on nasal septum 40,with delivery portion 1306 located against the nasal mucosa 32. Sensor1302 may sense a parameter from the tissue (for example, a chemicalparameter such as a glucose concentration, a heart rate or bloodpressure parameter, or a temperature, among others). Control signalgeneration circuitry 1304 may generate a delivery control signal basedupon a sense signal received from sensor 1302. The delivery controlsignal may be provided to delivery portion 1306, to drive delivery ofmaterial 1308.

In the controllable release nasal device depicted in FIG. 44, bothsensor 1302 and delivery portion 1306 are positioned adjacent to nasalmucosa 32. FIGS. 45, 46 and 47 depict other possible configurations forsensors and delivery portions of controllable release nasal devices.FIGS. 45 through 47 are cross-sectional views of a controllable releasenasal device in a nostril. In FIG. 45, sensor 1350 is positioned onstructural element 1352 so as to be positioned adjacent to the nasalmucosa 32 when structural element 1352 is mounted within the nasalregion of the subject. Delivery portion 1354 is positioned adjacentlumen 1356 of structural element 1352, away from nasal mucosa 32.Control signal generation circuitry 1358 is also indicated.Alternatively, as shown in FIG. 46, sensor 1350 may be positioned onstructural element 1352 so as to be positioned adjacent to lumen 1356when structural element 1352 is mounted within the nasal region of thesubject. In still other embodiments, as illustrated in FIG. 47, bothsensor 1350 and delivery portion 1354 may be positioned adjacent tolumen 1356 when structural element 1352 is mounted within the nasalregion of the subject.

Sensors used in the various embodiments described herein (e.g., sensors1074 and 1076 in FIG. 39, sensor 1302 in FIG. 44, or sensor 1350 inFIGS. 45-47) may be of various types, including, for example pressuresensors, temperature sensors, flow sensors, or chemical sensors, forexample. Sensors may be used to detect a condition of interest in thefluid (e.g. gas and/or liquid droplets or small solid particles) withina lumen of the nasal cavity (or lumen of a delivery device continuoustherewith), or in tissue surrounding the lumen, which may include, forexample, detecting pressure, temperature, fluid flow, presence of a cellof interest, or concentration of a chemical or chemical species(including ionic species) of interest. A sensor may sense a wide varietyof physical or chemical properties. In some embodiments, detecting acondition of interest may include detecting the presence (or absence) ofa material or structure of interest in the fluid. A sensor may includeone or more of an optical sensor, an imaging device, an acoustic sensor,a pressure sensor, a temperature sensor, a flow sensor, a viscositysensor, or a shear sensor for measuring the effective shear modulus ofthe fluid at a frequency or strain-rate, a chemical sensor fordetermining the concentration of a chemical compound or species, abiosensor, or an electrical sensor, for example. An optical sensor maybe configured to measure the absorption, emission, fluorescence, orphosphorescence of at least a portion of the fluid, for example. Suchoptical properties may be inherent optical properties of all or aportion of the fluid, or may be optical properties of materials added orintroduced to the fluid, such as tags or markers for materials ofinterest within the fluid. A biosensor may detect materials including,but not limited to, a biological marker, an antibody, an antigen, apeptide, a polypeptide, a protein, a complex, a nucleic acid, a cell orcell fragment (and, in some cases, a cell of a particular type, e.g. bymethods used in flow cytometry), a cellular component, an organelle, apathogen, a lipid, a lipoprotein, an alcohol, an acid, an ion, animmunomodulator, a sterol, a carbohydrate, a polysaccharide, aglycoprotein, a metal, an electrolyte, a metabolite, an organiccompound, an organophosphate, a drug, a therapeutic, a gas, a pollutant,or a tag. A biosensor may include an antibody or other reasonablyspecific binding molecule such as a receptor or ligand. A sensor mayinclude a single sensor or an array of sensors, and is not limited to aparticular number or type of sensors. A sensor might comprise in part orwhole, a gas sensor such as an acoustic wave, chemiresistant, orpiezoelectric sensor, or perhaps an “electronic nose”. A sensor may bevery small, comprising a sensor or array that is a chemical sensor(“Chemical Detection with a Single-Walled Carbon Nanotube Capacitor”, E.S. Snow, Science, Vol. 307, pp. 1942-1945, 2005.), a gas sensor (“Smartsingle-chip gas sensor microsystem”, Hagleitner, C. et al., Nature, Vol.414 pp. 293-296, 2001.), an electronic nose, a nuclear magneticresonance imager (“Controlled multiple quantum coherences of nuclearspins in a nanometre-scale device”, Go Yusa, Nature, Vol. 343: pp.1001-1005, 2005). Further examples of sensors are provided in TheBiomedical Engineering Handbook, Second Edition, Volume I, J. D.Bronzino, Ed., Copyright 2000, CRC Press LLC, pp. V-1-51-9, and U.S.Pat. No. 6,802,811, both of which are incorporated herein by reference.A sensor may be configured to measure various parameters, including, butnot limited to, the electrical resistivity of the fluid, the density orsound speed of the fluid, the pH, the osmolality, or the index ofrefraction of the fluid at at least one wavelength, as well as itstemperature, water content and chemical composition. The selection of asuitable sensor for a particular application or use site is consideredto be within the capability of a person having skill in the art. In someapplications, detecting a condition of interest in the fluid may includedetecting the presence of a material of interest in the fluid (gasand/or liquid) within a nasal lumen. A material of interest in a fluidmay include, dust particle, a pollen particle, a pathogen, or parasite,or a cell, cellular component, or collection or aggregation of cells orcomponents thereof.

A controllable release nasal device may include an active portion whichmay perform an action in the nasal cavity in addition to or instead ofthe material release function performed by the release portion describedherein. A release portion is an exemplar of an active portion. A numberof active portions are described, for example, in U.S. patentapplication Ser. No. 11/403,230, entitled “Lumenally Active Device” andfiled Apr. 12, 2006, which is incorporated herein by reference above.

In connection with detection of the presence of a material of interest,for example, an active portion of the controllable release nasal systemmay be capable of removing, modifying, or destroying the material ofinterest. Modification or destruction of the material of interest may beaccomplished by the release of a suitable material (e.g. anendopeptidatse for killing bacteria, or an anti-inflammatory,biomimetic, or biologic to bind to and inactivate an inflammatorymediator such as histamine or an immunoglobulin), by the delivery ofsuitable energy (e.g., acoustic energy, electromagnetic energy such aslight to cause a photoreaction, break bonds in molecule, produceheating, etc., or by delivery of heat or cold or other chemo-physicalchange (e.g. ambient pressure, pH, osmolality, toxic materialintroduction/generation) for tissue modification or ablation.

FIGS. 48 through 55 illustrate examples of different active portionswhich may be included in a controllable release nasal device or system.The active portion may include a heating element 1400 as depicted inFIG. 48, operatively coupled to the response initiation circuitry 1401and configured to produce heating in response to detection of thecondition of interest. The heating element may be a resistive elementthat produces heat when current is passed through it, or it may be amagnetically active material that produces heat upon exposure to anelectromagnetic field. Examples of magnetically active materials includepermanently magnetizable materials, ferromagnetic materials such asiron, nickel, cobalt, and alloys thereof, ferrimagnetic materials suchas magnetite, ferrous materials, ferric materials, diamagnetic materialssuch as quartz, paramagnetic materials such as silicate or sulfide, andantiferromagnetic materials such as canted antiferromagnetic materialswhich behave similarly to ferromagnetic materials; examples ofelectrically active materials include ferroelectrics, piezoelectrics anddielectrics.

Alternatively, the active portion may include a cooling element 1402 asdepicted in FIG. 49, operatively coupled to the response initiationcircuitry 1403 and configured to produce cooling in response todetection of the condition of interest. Cooling may be produced by anumber of mechanisms and/or structures. For example, cooling may beproduced by an endothermic reaction (such as the mixing of ammoniumnitrate and water) initiated by opening of a valve or actuation of acontainer in response to a control signal. Other methods and/ormechanisms of producing cooling may include, but are not limited to,thermoelectric (e.g., Peltier Effect) and liquid-gas-vaporization (e.g.,Joule-Thomson) devices.

In some embodiments, the active portion may include an electromagneticradiation source 1404 as depicted in FIG. 50, operatively coupled to theresponse initiation circuitry 1405 and configured to emitelectromagnetic radiation in response to detection of the condition ofinterest. Electromagnetic radiation sources may include light sources,for example, such as light emitting diodes and laser diodes, or sourcesof other frequencies of electromagnetic energy or radiation, radiowaves, microwaves, ultraviolet energy, infrared energy, optical energy,terahertz radiation, and the like. In some embodiments, the activeportion may include an electric field source or a magnetic field source.

As another alternative, the active portion may include an acousticenergy source 1406 (e.g., a piezoelectric crystal) as depicted in FIG.51, operatively coupled to the response initiation circuitry 1407 andconfigured to emit acoustic energy in response to detection of thecondition of interest. The active portion may include a pressure sourceoperatively coupled to the response initiation circuitry and configuredto apply pressure to a portion of the body lumen in response todetection of the condition of interest. Pressure sources may includematerials that expand through absorption of water, or expand or contractdue to generation or consumption of gas or conformation change producedby chemical reactions or temperature changes, electrically-engenderedMaxwell stresses, osmotic stress-generators, etc. FIG. 52 depicts anegative pressure source 1450 capable of applying negative pressure (inthis example, substantially radially-inward force) to lumen walls 1451,while FIG. 53 depicts a positive pressure (expanding or expansion)source 1452, capable of applying positive pressure (in this example, asubstantially radially-outward force) to lumen walls 1451.

Alternatively, or in addition, in some embodiments the active portionmay include a capture portion operatively coupled to the responseinitiation circuitry and configured to capture the detected material ofinterest. FIG. 54 depicts a device 1500 including a fluid captureportion 1506. Delivery device 1500 includes sensor 1502, responseinitiation circuitry 1504, and fluid capture portion 1506. Fluid entersfluid capture portion 1506 via inlet 1508. Fluid capture portion 1506may be a reservoir, for example, into which fluid is drawn by capillaryaction. Alternatively, fluid may be pumped into capture portion 1506.Captured fluid may be treated and released, or simply stored. In someapplications, stored fluid may be subjected to analysis.

FIG. 55 depicts delivery device 1550 including a sample collectionstructure 1552 capable of collecting a solid sample 1554. In the exampledepicted in FIG. 55, solid sample 1554 is a solid material found upon orimmediately under the surface of the lumen-defining wall 1556 (a nasalpolyp or inflammed tissue biopsy sample, for example). Solid sample 1554placed in storage reservoir 1558 by sample collection structure 1552. Ina related alternative embodiment, a delivery device may include a filteror selective binding region to remove materials from fluid moving pastor through the delivery device.

FIG. 56 is a flow diagram of a method of delivering a material to thenasal region of a subject. As indicated at 1602, the method may includethe step of releasing at least one material from a delivery portion of adelivery device mounted within a nasal region of a subject in responseto a delivery control signal corresponding to a desired release pattern.

The method may include including transmitting information relating tothe operation of the delivery device to are mote location, which mayinclude, for example, information relating to the delivery of materialby the delivery device. The method may include transmitting informationrelating to one or more sensed values of the parameter of interest to aremote location.

As shown in FIG. 57, in addition to releasing at least one material froma delivery portion of a delivery device mounted within a nasal region ofa subject in response to a delivery control signal corresponding to adesired release pattern at 1654, the method may include the additionalsteps of sensing at least one parameter of interest in the nasal regionwith a sensor in the delivery device at 1652, and controlling therelease of the at least one material based upon the value of the atleast one parameter of interest at 1656. The method may include sensingthe at least one parameter of interest from tissue in the nasal region,as shown at 1660, sensing the at least one parameter of interest fromblood in the nasal region, as shown at 1662, or sensing the at least oneparameter of interest from a gas or gaseous mixture within a nasalcavity or nostril, as shown at 1664.

As shown in FIG. 58, other method steps may include a number ofalternative method steps for generating a delivery control signal. Asshown at step 1702, the method may include generating the deliverycontrol signal with a control signal generation circuitry in a remotedevice and transmitting the delivery control signal to the deliverydevice. Alternatively, as shown at step 1704, the method may includegenerating the delivery control signal with control signal generationcircuitry in the delivery device, or generating the delivery controlsignal with control signal generation circuitry located at least in partat a location remote from the delivery portion of the delivery device,shown at step 1706. Any of steps 1702 through 1706 may be followed by astep of releasing at least one material from a delivery portion of adelivery device mounted within a nasal region of a subject in responseto a delivery control signal corresponding to a desired release pattern,as indicated at step 1708.

As shown in FIG. 59, the method may include the steps of sensing atleast one parameter of interest in the nasal region with a sensor in thedelivery device at 1752, storing a record of at least one sensed valueof the at least one parameter of interest at 1754, and releasing atleast one material from a delivery portion of a delivery device mountedwithin a nasal region of a subject in response to a delivery controlsignal corresponding to a desired release pattern at 1756, includingcontrolling the release of the at least one material based upon thevalue of the at least one parameter of interest at 1758.

Some embodiments of the method may include generating a delivery controlsignal at least in part as a function of the individual identity of thesubject.

As shown in FIG. 60, the method may include receiving the at least onematerial from at least one source located remote from the deliveryportion of the delivery device at step 1802, and releasing at least onematerial from a delivery portion of a delivery device mounted within anasal region of a subject in response to a delivery control signalcorresponding to a desired release pattern at 1804.

A shown in FIG. 61, releasing at least one material from a deliveryportion of a delivery device mounted within a nasal region of a subjectin response to a delivery control signal corresponding to a desiredrelease pattern at 1852 may include releasing at least one materialincluding a systemically active material, as indicated at 1854,releasing at least one material include a material having local activityin the nasal region, nasopharynx, or pulmonary region, as indicated at1856 releasing at least one material including an odorant, an aroma, anolfactory modulator or a scented material, as indicated at 1858, orreleasing at least one material including one or more neurotransmittersor neurotransmitter inhibitors, as indicated at 1860.

In some embodiments, as shown in FIG. 62, the method may includecalculating the delivery control signal based upon one or more storedparameters, at 1902, and releasing at least one material from a deliveryportion of a delivery device mounted within a nasal region of a subjectin response to the delivery control signal corresponding to a desiredrelease pattern at 1904.

In an embodiment as shown in FIG. 63, in addition to the steps ofcalculating the delivery control signal based upon one or more storedparameters, at 1906, and releasing at least one material from a deliveryportion of a delivery device mounted within a nasal region of a subjectin response to a delivery control signal corresponding to a desiredrelease pattern at 1908, the method may include storing the one or morestored parameters in the delivery device prior to generation of thedelivery control signal, as shown at step 1904. The one or more storedparameters may be received from an input device operatively connected tothe delivery device, at step 1902. For example, the method may includereceiving the one or more stored parameters from the input device via anoptical connection, as shown at 1910, receiving the one or more storedparameters from the input device via a wired connection, as shown at1912, or receiving the one or more stored parameters from the inputdevice via a wireless connection, as shown at 1914. In otherembodiments, the method may instead (or in addition) include calculatingthe delivery control signal based upon one or more prior values of thedelivery control signal.

As shown in FIG. 64, one embodiment of the method may include generatingthe delivery control signal from a stored release pattern, at step 1952,before releasing at least one material from a delivery portion of adelivery device mounted within a nasal region of a subject in responseto a delivery control signal corresponding to a desired release patternat step 1954. As shown in FIG. 65, in addition to generating thedelivery control signal from a stored release pattern, at step 2006, andreleasing at least one material from a delivery portion of a deliverydevice mounted within a nasal region of a subject in response to adelivery control signal corresponding to a desired release pattern atstep 2008, the method may include a step of storing the release patternin the delivery device prior to generation of the delivery controlsignal, at step 2004. The method may also include a step of receivingthe release pattern from an input device operatively connected to thedelivery device, at 2002, for example, by receiving the release patternfrom the input device via an optical connection, as indicated at 2010,receiving the release pattern from the input device via a wiredconnection, as indicated at 2012, or receiving the release pattern fromthe input device via a wireless connection, as indicated at 2014.

Methods of using devices and systems as described herein may include notonly the use of the device while it is mounted within the nasal regionof a subject, but may also include steps of mounting at least a portionof the delivery device within the nasal region of the subject, andoptionally, removing at least a portion of the delivery portion of thedelivery device from the nasal region of the subject following a useperiod. It will be appreciated that for short use periods, a method mayinclude mounting at least a portion of the delivery device within thenasal region of the subject prior to releasing the at least one materialfrom the delivery portion of the delivery device and removing at leastthe delivery portion of the delivery device from the nasal region of thesubject following a use period. On the other hand, in applications wherethe device is mounted in the nasal region of the subject substantiallypermanently, the device may be mounted in the nasal region, and no stepstaken to remove the device. In some cases, the device may be mountedmanually, by the subject, or by someone acting on behalf of the subject,for example a medical care provider. In some cases, the emplacement ofthe device within the nasal region may performed with the use of aninstallation device, such as a tool that will hold the device to allowit to be inserted into portions of the nasal region that would otherwisebe inaccessible. Local or general anesthetic may be provided in certaincases, as appropriate to provide for the comfort of the subject.

According to various embodiments, a controllable release nasal systemmay include software for controlling the release of material from adelivery device mounted within a nasal region of a subject. Suchsoftware is illustrated in a block diagram in FIG. 66. The basiccomponents of the controllable release nasal system 2050 may includesoftware 2052, at least one sensor 2054, a delivery portion 2056, and auser input device 2058. Non-software components are described elsewhereherein. Software 2052 may include a control signal generation module2060 capable of generating a delivery control signal corresponding to adesired pattern of delivery of a material into a nasal region of asubject from a delivery portion of the delivery device mounted withinthe nasal region of the subject, according to a model of the entiresystem. Software 2052 may include at least one of a data storage module2062 capable of storing pattern data or pattern parameters representingthe desired pattern of delivery of the material into the nasal region ofthe subject or a sensing module 2064 capable of receiving and processinga sense signal from a sensor portion of the delivery device, wherein thecontrol signal generation module is configured to generate the deliverycontrol signal based upon at least one of the pattern data, patternparameters or sense signal, generally proceeding according to a model.In another aspect, the software may include both a data storage module2062 capable of controlling storage of pattern data or patternparameters representing the desired pattern of delivery of the materialinto the nasal region of the subject according to a model and a sensingmodule 2064 capable of receiving and processing a sense signal from asensor portion 2054 of the delivery device.

Data storage module 2062 may be capable of storing a sense signalreceived from the sensing module 2064. The sense signal may be aprocessed sense signal from the sensor portion 2054 of the deliverydevice. The software may include a data storage module 2062 configuredto store one or more values from the delivery device.

At least a portion of the one or more values may be sense signal valuesreceived from the sensing module 2064. Alternatively, or in addition, atleast a portion of the one or more values are sense parameters receivedfrom the sensing module 2064. In some embodiments, at least a portion ofthe one or more values may be delivery control signal values from thecontrol signal generation module 2060.

In another aspect, the software may include a user interface module 2066configured to receive user input of one or more user-enterableparameters from a user interface device. The software may include a userinterface module 2066 configured to receive user input of a desireddelivery pattern from a user interface device 2058. In some embodiments,the user interface module may be configured to receive the desireddelivery pattern in the form of a digital data transmission.

The software may include a sensing module 2064 capable of receiving andprocessing a sense signal from a sensor portion 2054 of the deliverydevice. The sensing module 2064 may be capable of processing the sensesignal by various signal processing methods as are known to those ofskill in the art, including, but not limited to filtering, windowing,noise reduction, signal averaging, feature detection, time-domainanalysis, frequency domain analysis, feature extraction, comparison ofthe sense signal with, e.g., a template sense signal, sorting, datareduction, or endpoint determination.

In some embodiments, the control signal generation module 2060 may becapable of generating the delivery control signal by calculating thedelivery control signal based upon one or more stored parameters. Insome embodiments, at least a portion of the stored parameters may bespecific to the subject, relating to size, weight, age, gender, medicalor health status, and so forth. The control signal generation module2060 may be capable of generating the delivery control signal from astored release pattern. The parameters or release pattern may be storedin a data storage location under the control of data storage module2062.

Delivery devices and systems as described herein may be operated underthe control of software. Certain components of system 2050 may beprimarily hardware-based, e.g., sensor portion 2054, delivery portion2056, and, optionally, user interface device 2058. Hardware-baseddevices may include components that are electrical, mechanical,chemical, optical, electromechanical, electrochemical, electro-optical,and are not limited to the specific examples presented herein. Controlsignal generation module 2060, data storage module 2062, sensing module2064, and use interface module 2066 may be all or mostly software-based;however, it will be appreciated that various operations may be performedin hardware, software, firmware, or various combinations thereof.

Those having skill in the art will recognize that the state of the arthas progressed to the point where there is little distinction leftbetween hardware and software implementations of aspects of systems; theuse of hardware or software is generally (but not always, in that incertain contexts the choice between hardware and software can becomesignificant) a design choice representing cost vs. efficiency tradeoffs.Those having skill in the art will appreciate that there are variousvehicles by which processes and/or systems and/or other technologiesdescribed herein can be effected (e.g., hardware, software, and/orfirmware), and that the preferred vehicle will vary with the context inwhich the processes and/or systems and/or other technologies aredeployed. For example, if an implementer determines that speed andaccuracy are paramount, the implementer may opt for a mainly hardwareand/or firmware vehicle; alternatively, if flexibility is paramount, theimplementer may opt for a mainly software implementation; or, yet againalternatively, the implementer may opt for some combination of hardware,software, and/or firmware. Hence, there are several possible vehicles bywhich the processes and/or devices and/or other technologies describedherein may be effected, none of which is inherently superior to theother in that any vehicle to be utilized is a choice dependent upon thecontext in which the vehicle will be deployed and the specific concerns(e.g., speed, flexibility, or predictability) of the implementer, any ofwhich may vary. Those skilled in the art will recognize that opticalaspects of implementations will typically employ optically-orientedhardware, software, and or firmware.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples.

Insofar as such block diagrams, flowcharts, and/or examples contain oneor more functions and/or operations, it will be understood by thosewithin the art that each function and/or operation within such blockdiagrams, flowcharts, or examples can be implemented, individuallyand/or collectively, by a wide range of hardware, software, firmware, orvirtually any combination thereof. In one embodiment, several portionsof the subject matter described herein may be implemented viaApplication Specific Integrated Circuits (ASICs), Field ProgrammableGate Arrays (FPGAs), digital signal processors (DSPs), or otherintegrated formats. However, those skilled in the art will recognizethat some aspects of the embodiments disclosed herein, in whole or inpart, can be equivalently implemented in integrated circuits, as one ormore computer programs running on one or more computers (e.g., as one ormore programs running on one or more computer systems), as one or moreprograms running on one or more processors (e.g., as one or moreprograms running on one or more microprocessors), as firmware, or asvirtually any combination thereof, and that designing the circuitryand/or writing the code for the software and or firmware would be wellwithin the skill of one of skill in the art in light of this disclosure.In addition, those skilled in the art will appreciate that themechanisms of the subject matter described herein are capable of beingdistributed as a program product in a variety of forms, and that anillustrative embodiment of the subject matter described herein appliesregardless of the particular type of signal bearing medium used toactually carry out the distribution. Examples of a signal bearing mediuminclude, but are not limited to, the following: a recordable type mediumsuch as a floppy disk, a hard disk drive, a Compact Disc (CD), a DigitalVideo Disk (DVD), a digital tape, a computer memory, etc.; and atransmission type medium such as a digital and/or an analogcommunication medium (e.g., a fiber optic cable, a waveguide, a wiredcommunications link, a wireless communication link, etc.).

In a general sense, those skilled in the art will recognize that thevarious embodiments described herein can be implemented, individuallyand/or collectively, by various types of electromechanical systemshaving a wide range of electrical components such as hardware, software,firmware, or virtually any combination thereof; and a wide range ofcomponents that may impart mechanical force or motion such as rigidbodies, spring or torsional bodies, hydraulics, and electro-magneticallyactuated devices, or virtually any combination thereof. Consequently, asused herein “electromechanical system” includes, but is not limited to,electrical circuitry operably coupled with a transducer (e.g., anactuator, a motor, a piezoelectric crystal, etc.), electrical circuitryhaving at least one discrete electrical circuit, electrical circuitryhaving at least one integrated circuit, electrical circuitry having atleast one application specific integrated circuit, electrical circuitryforming a general purpose computing device configured by a computerprogram (e.g., a general purpose computer configured by a computerprogram which at least partially carries out processes and/or devicesdescribed herein, or a microprocessor configured by a computer programwhich at least partially carries out processes and/or devices describedherein), electrical circuitry forming a memory device (e.g., forms ofrandom access memory), electrical circuitry forming a communicationsdevice (e.g., a modem, communications switch, or optical-electricalequipment), and any non-electrical analog thereto, such as optical orother analogs. Those skilled in the art will recognize thatelectromechanical as used herein is not necessarily limited to a systemthat has both electrical and mechanical actuation except as context maydictate otherwise. Non-electrical analogs of electrical circuitry mayinclude fluid circuitry, electromechanical circuitry, mechanicalcircuitry, and various combinations thereof.

In a general sense, those skilled in the art will recognize that thevarious aspects described herein which can be implemented, individuallyand/or collectively, by a wide range of hardware, software, firmware, orany combination thereof can be viewed as being composed of various typesof “electrical circuitry.” Consequently, as used herein “electricalcircuitry” includes, but is not limited to, electrical circuitry havingat least one discrete electrical circuit, electrical circuitry having atleast one integrated circuit, electrical circuitry having at least oneapplication specific integrated circuit, electrical circuitry forming ageneral purpose computing device configured by a computer program (e.g.,a general purpose computer configured by a computer program which atleast partially carries out processes and/or devices described herein,or a microprocessor configured by a computer program which at leastpartially carries out processes and/or devices described herein),electrical circuitry forming a memory device (e.g., forms of randomaccess memory), and/or electrical circuitry forming a communicationsdevice (e.g., a modem, communications switch, or optical-electricalequipment). Those having skill in the art will recognize that thesubject matter described herein may be implemented in an analog ordigital fashion or some combination thereof.

One skilled in the art will recognize that the herein describedcomponents (e.g., steps), devices, and objects and the discussionaccompanying them are used as examples for the sake of conceptualclarity and that various configuration modifications are within theskill of those in the art. Consequently, as used herein, the specificexemplars set forth and the accompanying discussion are intended to berepresentative of their more general classes. In general, use of anyspecific exemplar herein is also intended to be representative of itsclass, and the non-inclusion of such specific components (e.g., steps),devices, and objects herein should not be taken as indicating thatlimitation is desired.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations are not expressly set forth herein for sakeof clarity.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely exemplary, and that in fact many other architectures can beimplemented which achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “associated with” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected”, or“operably coupled”, to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably couplable”, to each other to achieve the desiredfunctionality. Specific examples of operably couplable include but arenot limited to physically mateable and/or physically interactingcomponents and/or wirelessly interactable and/or wirelessly interactingcomponents and/or logically interacting and/or logically interactablecomponents.

While particular aspects of the present subject matter described hereinhave been shown and described, it will be apparent to those skilled inthe art that, based upon the teachings herein, changes and modificationsmay be made without departing from the subject matter described hereinand its broader aspects and, therefore, the appended claims are toencompass within their scope all such changes and modifications as arewithin the true spirit and scope of the subject matter described herein.Furthermore, it is to be understood that the invention is defined by theappended claims. It will be understood by those within the art that, ingeneral, terms used herein, and especially in the appended claims (e.g.,bodies of the appended claims) are generally intended as “open” terms(e.g., the term “including” should be interpreted as “including but notlimited to,” the term “having” should be interpreted as “having atleast,” the term “includes” should be interpreted as “includes but isnot limited to,” etc.). It will be further understood by those withinthe art that if a specific number of an introduced claim recitation isintended, such an intent will be explicitly recited in the claim, and inthe absence of such recitation no such intent is present. For example,as an aid to understanding, the following appended claims may containusage of the introductory phrases “at least one” and “one or more” tointroduce claim recitations. However, the use of such phrases should notbe construed to imply that the introduction of a claim recitation by theindefinite articles “a” or “an” limits any particular claim containingsuch introduced claim recitation to inventions containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., “a system having at leastone of A, B, or C” would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that virtually any disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms. For example, the phrase “A or B” will be understood toinclude the possibilities of “A” or “B” or “A and B.”

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

1.-125. (canceled)
 126. A controllable release nasal system, comprising:a structural element including at least one positioning portionconfigured for contacting an interior surface of a nasal region andmounting the structural element within the nasal region of a subject; adelivery portion mounted relative to the structural element andconfigured to release at least one material responsive to a deliverycontrol signal; control signal generation circuitry configured togenerate a delivery control signal corresponding to a desired pattern ofrelease of the at least one material into the nasal region; and a powersource for providing power to one or more components of the controllablerelease nasal system.
 127. The system of claim 126, wherein the powersource includes at least one of a battery, a microbattery, a powerreceiver capable of receiving inductively coupled power from an externalpower source, a fuel cell, a biofuel cell, or a mechanical energystorage structure.
 128. The system of claim 126, wherein the controlsignal generation circuitry is located on the structural element. 129.The system of claim 126, wherein the control signal generation circuitryis located remote from the structural element and is associated with atransmitting structure capable of transmitting the delivery controlsignal to the structural element, and wherein the delivery portion isassociated with a receiving structure capable of receiving the deliverycontrol signal.
 130. The system of claim 126, wherein the control signalgeneration circuitry includes at least one of a microprocessor,hardware, software, or firmware.
 131. The system of claim 126, whereinthe control signal generation circuitry is configured to generate adelivery control signal based upon a pre-determined delivery pattern orcalculated from one or more stored parameters.
 132. The system of claim131, including a memory location for storing the predetermined deliverypattern or the one or more stored parameters.
 133. The system of claim126, wherein the control signal generation circuitry is configured togenerate a delivery control signal corresponding to a pattern ofdelivery of the at least one material expected to produce at least oneof a therapeutic effect or a sensory effect.
 134. A controllable releasenasal system, comprising: a structural element including at least onepositioning portion configured for contacting an interior surface of anasal region of a subject and mounting the structural element within thenasal region of the subject; a delivery portion mounted relative to thestructural element and configured to release at least one materialresponsive to a delivery control signal; a sensor capable of detectingor measuring a parameter of interest in the nasal region of the subject;and control signal generation circuitry configured to generate adelivery control signal corresponding to a desired pattern of release ofthe at least one material into the nasal region.
 135. The system ofclaim 134, wherein the control signal generation circuitry is configuredto calculate the delivery control signal based at least in part on oneor more parameters of interested detected or measured by the sensor.136. The system of claim 134, wherein the control signal generationcircuitry is configured to modulate generation of the delivery controlsignal based upon at least one parameter of interest detected ormeasured by the sensor.
 137. The system of claim 134, wherein the sensoris positioned on the structural element so as to be positioned adjacentto the nasal mucosa when the structural element is mounted within thenasal region of the subject.
 138. The system of claim 134, wherein thesensor is positioned on the structural element so as to be positionedadjacent to the lumen of the nasal cavity when the structural element ismounted within the nasal region of the subject.
 139. The system of claim134, wherein the wherein the sensor includes at least one pressuresensor, temperature sensor, moisture sensor, flow sensor, strain sensor,chemical sensor, biosensor, optical sensor, imaging device, or acousticsensor.
 140. A method of delivering a material to the nasal region of asubject, comprising: sensing at least one parameter of interest in thenasal region of the subject with a sensor in the delivery device mountedwithin the nasal region; generating a delivery control signalcorresponding to a desired release pattern of at least one material froma delivery portion of the delivery device based upon the value of theparameter of interest; and releasing the at least one material from thedelivery portion of the delivery device in response to the deliverycontrol signal.
 141. The method of claim 140, including transmitting atleast one of information relating to the operation of the deliverydevice, information relating to the delivery of material by the deliverydevice, or information relating to one or more sensed values of theparameter of interest to a remote location.
 142. The method of claim140, including sensing the at least one parameter of interest fromtissue in the nasal region, blood in the nasal region, or a gas orgaseous mixture within a nasal cavity or nostril.
 143. The method ofclaim 140, including generating the delivery control signal with controlsignal generation circuitry located at least in part at a locationremote from the delivery portion of the delivery device.
 144. The methodof claim 140, including generating the delivery control signal withcontrol signal generation circuitry in the delivery device.
 145. Themethod of claim 140, including storing a record of at least one sensedvalue of the at least one parameter of interest.
 146. The method ofclaim 140, including calculating the delivery control signal based uponone or more prior values of the delivery control signal, calculating thedelivery control signal based upon one or more stored parameters, orgenerating the delivery control signal from a stored release pattern.147. The method of claim 146, including storing the one or more storedparameters or the release pattern in the delivery device prior togeneration of the delivery control signal.
 148. The method of claim 147,including receiving the one or more stored parameters or the releasepattern from an input device operatively connected to the deliverydevice.
 149. The method of claim 148, including receiving the one ormore stored parameters or the release pattern from the input device viaa connection selected from an optical connection, a wired connection, ora wireless connection.